We have analyzed Hungtington's chorea and an autosomal dominant Alzheimer's fibroblast cell lines in culture matched for age, sex, passage number and growth rate with normal and find striking differences in protein glycosylation. We propose to extend these studies by the following objectives and methods. Collect fibroblast cultures from 25 Huntington's and 25 normal (to include autosomal dominant mutations) matched for age, sex, passage number and growth rate. Determine the hexosamine pool size in Huntington's chorea and normal fibroblasts. The fibroblasts are labeled to constant specific activity by 32P followed by a 48 hour pulse with 14C GLcN. The acid soluble 14C hexosamine/ 32P hexosamine ratio is determined. Measure glycosylation of cellular and membrane glycoprotein by labelling the fibroblasts to constant specific activity with 14C glucose and analyzing 14C sialic acid and 14C hexosamine of macromolecules and the acid soluble fraction of cell extracts. A sensitive radioisotope assay for F-6-P glutamine transamidase and isoelectric focusing of its isoenzymes using labelled 14C F-6-P and isolating 14C glucosamine by charcoal adsorption followed by paper chromatography will be developed. The defect of fibroblast attachment to substratum and its nutritional correction is correlated to fibronectin on the plasma membrane and in culture media.